Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less
Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production ....Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production and the structure/function of the solar powerhouse of plants (chloroplasts), and addresses fundamental questions at the interface of biology and physics. The research explores chloroplasts as a manifestation of the all-pervading Second Law of Thermodynamics, advancing Australia's contribution to basic science and helping to train researchers.Read moreRead less
New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less
New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-lig ....New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-ligand interactions at increased rates and enhanced accuracy. In addition, the three-dimensional structures of proteins and protein domains of biologically important functions and unknown fold will be determined by NMR. The project aims at techniques of direct impact in pharmaceutical industry.Read moreRead less
Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin abso ....Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin absorbs light: e.g. intermediates such as metarhodopsin and opsin. The molecular knowledge obtained will help us to understand why it is that the visual system recovers so slowly after the eye has experienced very intense light.Read moreRead less
Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable ....Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable us to develop a computational model of the vascular wall and so predict how changes in electrical properties, as occur during pressure changes, can influence blood flow. Since ageing is accompanied by an increase in blood pressure, our results will contribute to a better understanding of blood flow regulation in our ageing population.Read moreRead less
Ionic Dispersion Forces in Physical Chemistry: Implications for pH, Electrochemistry, Nanoparticle Formation and Organic Synthesis. Our current understanding of charged systems in solution is deeply flawed . Existing theories are not predictive, mainly because they concentrate entirely on electrostatics. This proposal aims to partially rectify this by including the effects of previously neglected dispersion forces in a number of problems. These forces are responsible for much of the behaviou ....Ionic Dispersion Forces in Physical Chemistry: Implications for pH, Electrochemistry, Nanoparticle Formation and Organic Synthesis. Our current understanding of charged systems in solution is deeply flawed . Existing theories are not predictive, mainly because they concentrate entirely on electrostatics. This proposal aims to partially rectify this by including the effects of previously neglected dispersion forces in a number of problems. These forces are responsible for much of the behaviour seen in the following systems: the theory of electrolytes; electrochemistry pH and buffers; self energy effects in organic chemistry; and zeolite and nano-particle synthesis. The main outcome will be accurate and predictive theories for these systems.Read moreRead less
Design and Synthesis of Photoactive Peptides Based on Photosynthetic Reaction Centres. The aim of this proposal is to generate new and useful electron transfer components for biotechnological applications. We plan to design and synthesize artificial photoactive peptides inspired from natural photosynthetic reaction centres which capture the energy of light and convert it into usable forms of chemical energy. Our research will provide the ground work for the development of light-driven oxidation- ....Design and Synthesis of Photoactive Peptides Based on Photosynthetic Reaction Centres. The aim of this proposal is to generate new and useful electron transfer components for biotechnological applications. We plan to design and synthesize artificial photoactive peptides inspired from natural photosynthetic reaction centres which capture the energy of light and convert it into usable forms of chemical energy. Our research will provide the ground work for the development of light-driven oxidation-reduction catalysts that can be used in the production of clean fuels and chemical products.Read moreRead less
Comparative Biophysical Studies on Photosystem II of Higher Plants and Cyanobacteria. Photosystem II (PS-II) is one of two light trapping protein assemblies involved in the conversion of light into metabolic energy in all plants and algae. The manganese containing active site of PS-II is responsible for oxygen formation from water. The organisation and functioning of this centre and the detailed mechanism of photochemical energy conversion are not understood. This project will employ a combinati ....Comparative Biophysical Studies on Photosystem II of Higher Plants and Cyanobacteria. Photosystem II (PS-II) is one of two light trapping protein assemblies involved in the conversion of light into metabolic energy in all plants and algae. The manganese containing active site of PS-II is responsible for oxygen formation from water. The organisation and functioning of this centre and the detailed mechanism of photochemical energy conversion are not understood. This project will employ a combination of powerful biophysical techniques to probe the structure and mechanism of PS-II as a knowledge base for eventual genetic manipulation of plants and stategies for artificial photosynthesis.Read moreRead less
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less